Method of treatment of diarrhea in piglet of 2-4 weeks of age

ABSTRACT

DIARRHEA IN PIGLETS OF TWO TO FOUR WEEKS OF AGE IS SUCCESSFULLY TREATED WITH THE AID OF THERAPEUTIC COMPOSITION POSSESSING SPECIFIC ACTIVITY AGAINST SUCH PIGLEY DIARRHEA AND COMPRISING AS ACTIVE INGREDIENT BETAMETHASONE, DEXAMETHASONE, PREDNISOLONE PREDINSONE, PARAMETHASONE, METHLPREDNISOLONE, TRIAMCINOLONE, HYDROCORTISONE OR CORTISONE.

United States Patent Int. Cl. A61k1 7/12, 17/16 US. Cl. 424-243 9 Claims ABSTRACT OF THE DISCLOSURE Diarrhea in piglets of two to four Weeks of age is successfully treated with the aid of therapeutic compositions possessing specific activity against such piglet diarrhea and comprising as active ingredient betamethasone, dexamethasone, prednisolone prednisone, paramethasone, methylprednisolone, triamcinolone, hydrocortisone or cortisone.

This is a continuation-in-part application of applicants copending US. applications, Ser. No. 604,558, filed Dec. 27, 1966, and now abandoned.

This invention relates to the treatment of diarrhea in piglets of 2-4 weeks of age. More particularly, the present invention relates to treatment with the aid of a pharmaceutical composition containing adrenal corticoid as an active ingredient.

Recently, with increasing scale of pig breedings, it has become a serious problemboth in epidemiology and of enterprise for pig breedersthat suckling piglets of 2-4 weeks of age frequently suffer from specific diarrhea.

Generally, the problem essentially disappears with piglets of over five weeks of age.

In general, piglets farrowed normally from a sound dam grow favorably for the first week after birth but sometimes begin to excrete loose yellowish white feces at about the second week and then begin to have violent water diarrhea without color, which diarrhea is called milk scour or pig scour. Once the diarrhea breaks out, it spreads easily from piglet to piglet in a litter. The mortality from such diarrhea is estimated less than but sometimes mounts to 30% and the afflicted piglets, even if they survive do not grow favorably and finally set back in growth in that they suffer from chronic diarrhea. Consequently, such pigs may not be marketable.

For pig breeders, damage caused by such a diarrhea is so heavy, that available therapy has long been a desideratum. It has been known that administration of a certain kind of sulfa drug or antibiotic to the piglet of 2-4 weeks of age has some preventive efiects with respect of milk scour, however, such precedingly employed medicaments are not too effective for the therapeutic purpose in view and most of the once-afflicted piglets may not escape becoming a stunted growth pig.

At the period of disappearance of antibodies, derived from the colostrum, in the serum of a piglet of 2-4 weeks of age, certain strains of Escherichia coli proliferate rapidly in the duodenum and in the upper part of the small intestine, where a sort of endotoxin is produced. Thusproduced endotoxin is transferred into the serum through the intestinal walls and consequently provokes a reaction, which is thought to be a main cause of the 2-4 weeks piglet diarrhea. This type of diarrhea is clearly different etiologically, clinically and pathologically from so-called neonatal or new born colibacillosis which occurs in a piglet of 2-3 days of age. Moreover, for the purpose of inducing sows to farrow more frequently, pig breeders prefer to wean a piglet from the dam at an early time, namely, at about the fifteenth day of age, and such an 3,591,690 Patented July 6, 1971 early weaning tends to induce diarrhea symptoms in the piglet.

The object of the present invention is to provide a method of treating diarrhea in 2-4 Weeks piglets with the aid of therapeutic compositions possessing specific activities against such piglet diarrhea. The invention supplies a need in the pig industry and will represent a significant contribution to the development of such industry.

Active ingredients of the present invention are adrenal corticoids selected from the group consisting of betamethasone dexamethasone, prednisolone, prednisone, paramethasone, methylprednisolone, triamcinolone, hydrocortisone and cortisone. The pharmaceutical compositions can be formulated as powders, tablets, capsules, suspensions, injections and elixirs, and preferably as a syrup forms for the reason that pigs are generally fond of sweet taste.

According to this invention, it has been determined that the following values are substantially equivalent with regard to therapeutic effects against 2-4 weeks piglet diarrhea:

Milligrams Betamethasone 0.5-0.6 Dexamethasone 0.75 Prednisolone 5.0 Prednisone 5.0 Paramethasone 1.5-2.0 Methylprednisolone 4.0 Triamcinolone 4.0 Hydrocortisone 20.0 Cortisone 25.0

Further, therapeutic dosages of the active ingredients are as follows:

Single dosage per piglet per kilogram of body weight per day Milligrams Betamethasone 0.1-0.5 Dexamethasone 0.1-0.75 Prednisolone 1.0-5.0 Prednisone 1.0-5.0 Paramethasone 0.3-1.5 Triamcinolone 0.5-4.0 Methylprednisolone 0.5-4.0 Hydrocortisone 5.0-25.0 Cortisone 5.0-25.0

The afflicted piglets generally recover from the diarrhea upon administration of the above dosage of active ingredients for one to six days.

Typical examples are shown below:

Therapeutic elfects are based on observation of the following points.

State of faeces:

(a) Normal stoolof which shape was not destroyed.

(b) Loose stool-of which shape was destroyed a little but not far spread.

(c) Diarrhea stool-of which shape was destroyed and spread or was liquid. Appearance of buttocks:

Presence or absence of diarrhea was indicated by the dampness and contamination conditions around the anus and perineum.

Example 1.-Administration of betamethasone (a) Oral administration.-A syrup which was prepared so as to contain 1 mg. of betamethasone in 1 ml., was administered to piglets of 14-22 days of age which had had the diarrhea for 3-8 hours. A single dose per pig was 0.5 mg. and was administered once or twice per day for 1-4 days according to symptoms. Observation was made for six days.

Dose (0.5 mg/pig) No. of Days Once/ Onee/ Twice/ Twiee/ Twice/ N0. of Ratio of afliicted of day {or day or day for day for day for recovered effectiveness Race pigs age 1 day 2 days 2 days 3 days 4 days pigs (percent) Yorkshire 30 1422 8 9 2 1 29 96.6

1* YxL 45 -20 11 5 e 44 97.0

Landrace 9 14-19 8 1 0 100.0

For reference, three afiiicted but not medicated piglets For reference, three afllicted piglets of F YXL of 21 of F YxL of 15-20 days of age were observed Intervals days of age were administered a long acting sulfa drug of the diarrheas shortened gradually and the piglets died at after 1 hour from outbreak of diarrhea. Watery stools on the third day from outbreak of the diarrhea. didnt stop and the pigs became dehydrated states and (b) Intramuscular injection-A solution of betamethadi d on the fo rth day from the outbreak,

sone disodium phosphate, which was prepared as equiva- 15 (b) Intramuscular injection.A solution of prednisolent to 4 mg. of betamethasone in 1 ml. of sterile water, lone sodium hemisuccinate, which was prepared as equivawas injected to piglets of 12-21 days of age at after 3-5 lent to 20 mg. of prednisolone in 1 ml. of sterile water, hours from outbreak of the diarrhea. A single dose was was injected to piglets of 16-19 days of age at after equivalent to 0.1 mg. of betamethasone per kilograms 4-5 hours from outbreak of the diarrhea. A single dose of bodyweight per piglet. O

Dose (0.1 mg./kg.)

Once/ Once/ Twiee/ Twice/ No. of Days day day day day No. of Ratio of afilicted of for for for for recovered eflectiveuess Race pigs age 1 day 2 days 2 days 3 days pig (percent) Example 2.Administration of prednisolone per pig was equivalent to 10 mg. of prednisolone and was (a) Oral administration A syrup which was pm administered once or twice per day for 1-3 days.

Dose (10 rug/pig) Once/ Once/ Twice/ Twice/ Twice/ No. of Days day day day day day No. of Ratio of afilicted of for for for for for recovered effectiveness Race pigs age 1 day 2days 1 day 2days 3 days pigs (percent) F1 YXL 1e19 10 10 14 1 5 40 100.0

pared so as to contain 10 mg. of prednisolone in 1 ml., Example 3.Oral administration of dexamethasone was administered to piglets of 12-20 days of age at after 4-6 hours from outbreak of the diarrhea. A single A syrup which was prepared so as to contain 1 mg. of dose per piglet was 1-5 mg. per kilogram body-weight dexamethasone in 1 ml., was administered to piglets of according to symptoms and was administered once or 14-18 days of age at after 4 hours from outbreak of the twice per day for 1-3 days. Observation was made for diarrhea. A single dose per pig was equivalent to 0.2 mg. six days. per kilogram of body-weight.

Dose (0.2 mg./kg.

body-weight) Once/ Twice/ Twice/ No. of Days day day day No. of Ratio of aifiieted of for for for recovered effectiveness Race pigs age 1 day 1 day 2 days pigs (percent) F1 YxL 30 17 10 7 13 30 100.0 Yorkshire 20 19-20 20 10 J5. 0

Dose (1.5 mg./kg.)

Once/ Once/ Twicc/ 'lwice/ N0. of Days day day day day No. of Ratio of aillicted of [or or {or for recovered effectiveness Race pigs age lday 2days 2days 3 days pigs (percent) F1 YXL 12-16 10 43 5 2 59 98. 3 F YXLfl- 41 15-20 27 10 4 41 100.0

The group was chosen from pigs which had been medicated with sulfa drug at the period of 6-10 days of age for the preventive purpose but yet had the diarrhea.

Examples 4-8.Administrations of prednisone, paramethasone, triamcinolone, methylprednisolone and hydrocortisone Days of age at outbreak of diarrhea Sex Race

Landrace M Dose per kg. of body-weight per pig ter.

Orally, 1.0 lug/kg. of triamcinolone, 6 hours after the outbreak and the same dose 24 hours later.

Orally, 1.0 mg./kg. of triamcinolone, 24 hours after the outbreak and the same dose 12 hours later.

Orally, 3.0 mgJkg. of methylprednisolone States of diarrhea Normal stools were seen 8 hours after the medication.

Normal stools were seen 6 hours after the medication.

Normal stools were seen 7 hours after the medication.

Approximately loose stools were seen 7 hours and approximately normal stools 12 hours after the medication.

Loose stools were seen 7 hours and approximately normal stools 24 hours and normal stools 36 hours after the medication.

Loose stools were seen 10 hours and normal stools hours after the medication.

Normal stools were seen 6 hours after the General findings just after the outbreak.

24 hours later.

In addition to the above data, combined administration of the composition of the present invention and suitable sulfa drugs or antibiotics for piglets is recommended when the piglets are infected 'by other bacilli.

In each of the examples, M refers to Male, F refers to Female, and F YXL refers to the first filial generation born between female Yorkshire and male Landrace.

What is claimed is:

1. A method of treatment of diarrhea in a piglet of two to four weeks of age after birth which comprises administering to said alfiicted piglet an adrenal corticoid selected from the group consisting of 0.1-0.5 mg. of betamethasone,

0.1-0.75 mg. of dexamethasone,

1.0-5.0 mg. of prednisolone,

0.3-1.5 mg. of paramethasone,

0.5-4.0 mg. of triamcinolone,

1.0-5.0 mg. of prednisone,

0.5-4.0 mg. of methylprednisolone,

5.0-25.0 mg. of hydrocortisone, and

5 .O-25 .0 mg. of cortisone, in the form of a dosage unit, the amounts of the active ingredients being administered per kilogram of body weight of said piglet per day.

2. A method according to claim 1 wherein the active ingredient dexamethasone is administered in the amount of 0.1-0.75 mg.

3. A method according to claim 1 wherein the active ingredient prednisolone is administered in the amount of 1.0-5.0 mg.

Orally, 5.0 mgJkg. of hydrocortisone, 1 hour after the outbreak and the same dose medication.

Approximately loose stools were seen, which were changed to approximately normal stools 24 hours and normal stools were seen 48 hours after the medication.

Administered the drug in the form of mixture with sugar.

4. A method according to claim 1 wherein the active ingredient prednisone is administered in the amount of 1.0-5.0 mg.

5. A method according to claim 1 wherein the active lngredient paramethasone is administered in the amount of 0.3-1.5 mg.

6. A method according to claim 1 wherein the active ingredient triamcinolone is administered in the amount of 0.5-4.0 mg.

7. A method according to claim 1 wherein the active ingredient methylprednisolone is administered in the amount of 0.5-4.0 mg.

8. A method according to claim 1 wherein the active ingredient hydrocortisone is administered in the amount of 5.0-25.0 mg.

9. A method according to claim 1 wherein the active ingredient cortisone is administered in the amount of 5.0- 25.0 mg.

References Cited UNITED STATES PATENTS 2,607,716 8/1952 Link 424-631 OTHER REFERENCES Current Therapy, 1965, pp. 262-264.

SAM ROSEN, Primary Examiner 

